Journal article

Squalene Synthase Deficiency: Clinical, Biochemical, and Molecular Characterization of a Defect in Cholesterol Biosynthesis

David Coman, Lisenka ELM Vissers, Lisa G Riley, Michael P Kwint, Roxanna Hauck, Janet Koster, Sinje Geuer, Sarah Hopkins, Barbra Hallinan, Larry Sweetman, Udo FH Engelke, T Andrew Burrow, John Cardinal, James McGill, Anita Inwood, Christine Gurnsey, Hans R Waterham, John Christodoulou, Ron A Wevers, James Pitt



Mendelian disorders of cholesterol biosynthesis typically result in multi-system clinical phenotypes, underlining the importance of cholesterol in embryogenesis and development. FDFT1 encodes for an evolutionarily conserved enzyme, squalene synthase (SS, farnesyl-pyrophosphate farnesyl-transferase 1), which catalyzes the first committed step in cholesterol biosynthesis. We report three individuals with profound developmental delay, brain abnormalities, 2-3 syndactyly of the toes, and facial dysmorphisms, resembling Smith-Lemli-Opitz syndrome, the most common cholesterol biogenesis defect. The metabolite profile in plasma and urine suggested that their defect was at the level of squalene synt..

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Funding Acknowledgements

The authors would, first and foremost, like to thank the families, without whose participation this work would not have been possible. This work was supported by the Kevin Milo Trust and internal research funds at the Children's Hospital at Westmead. The authors would like to thank the Genome Aggregation Database (gnomAD) and the groups that provided exome and genome variant data to this resource. A full list of contributing groups can be found at The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program.